Emergency contraception (EC), i.e. contraceptive indicated for the prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure, is a woman's second chance for primary prevention of pregnancy.
For decades, various high-dose estrogen-progestin regimens have been prescribed by experienced gynecologists for EC, generally involving the off-label administration of high doses of combined oral contraceptive pills. It is only in the mid-nineteen-nineties that dedicated products appeared, following requests from regulatory agencies and women's groups for properly labelled and packaged preparations. Initially, dedicated products consisted of high-dose estrogen-progestin preparations. In 1999, based on WHO publications of randomized clinical trials demonstrating that 0.75 mg levonorgestrel twice was as effective as combined estrogen-progestin preparations, HRA Pharma's NorLevo® became the first progestin-only EC to be granted a marketing authorization in Western countries. Since that time, several preparations have been approved elsewhere in the world (e.g. Plan B®, Levonelle®, Postinor®), and currently the standard of care for EC within 72 hours of unprotected intercourse is the administration of 1.5 mg of levonorgestrel, either in a single dose or in two 0.75 mg doses taken 12-24 hours apart. A number of countries have granted non-prescription status to these preparations based on levonorgestrel's well-characterized safety profile and limited contraindications.
Although EC with 1.5 mg of levonorgestrel has undoubtedly contributed to the prevention of unwanted pregnancies, it has its limitations in terms of efficacy: its efficacy rate drops significantly with the time elapsed since unprotected intercourse. Reported pregnancy rates from WHO trials rise from approximately 1.5 to 2.6%, respectively, for intake 0 to 24 hrs as compared to intake 48-72 hrs after intercourse. In addition, for a woman who presents for EC more than 72 h after intercourse, the only available method with a proven efficacy is the insertion of a copper intra-uterine device (although not approved or labelled for such use in the United States), although use is limited by both availability and the need for insertion by a skilled health-care professional.
Obesity appears to significantly affect the therapeutic efficacy of oral contraceptives. For example, Holt et al. 2005 showed that being overweight increased the risk of becoming pregnant. Edelman et al. (2009) found that compared with woman having a normal body mass index, obese women had altered pharmacokinetics including half-life, clearance and time to reach steady state of the oral contraceptive. Obesity is an epidemic problem in many countries and especially within the United States. http://www.contraceptivetechnology.org/Trussell ContraceptionforObeseWomen.ppt—retrieved Dec. 13, 2009). Accordingly, there is a growing need to develop effective means of emergency contraception for obese women.
Ulipristal acetate (also referred to as CDB-2914, VA2914, HRP-2000 and RTI 3021-012) is an orally-active selective progesterone receptor modulator (SPRM) that has been developed for emergency contraception (EC). Ulipristal acetate inhibits or delays ovulation in a dose-dependent fashion (Stratton et al, 2000). In a double-blind non-inferiority trial, ulipristal acetate was shown to be as efficacious as levonorgestrel for preventing pregnancy when used within 72 hours of UPI (Creinin et al, 2006). Ulipristal acetate has been approved in Europe, under trademark EllaOne®, for use as an emergency contraceptive.